FIH Study of RGT-419B Alone and With Endocrine Therapy in HR-Positive, HER2-Negative Advanced/Metastatic Breast Cancer

First-in-Human, Escalating Oral Dose Study of RGT-419B Given Alone and With Endocrine Therapy in Subjects With Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Advanced/Metastatic Breast Cancer

This is a phase I, First-in-Human (FIH), open-label study to evaluate the safety, tolerability, pharmacokinetic (PK) profile, and preliminary efficacy of RGT-419B administered orally as monotherapy OR in combination with Hormonal Therapy in subjects with HR+, HER2- locally advanced and unresectable (Stage III) or metastatic (Stage IV) breast cancer whose disease has progressed during prior therapy with an approved CDK4/6i plus hormonal therapy.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: RGT-419B; Drug: RGT-419B in combination with hormonal therapy

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Joanna Dojillo, MSc; Phone Number: 617-315-9070; Email: joanna.dojillo@regor.com
• Study Contact Backup: Name: Regor Pharmaceuticals Central Office; Phone Number: 617-315-9070; Email: rgt-419b_01-101@regor.com

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • University of California, San Diego
      • Contact: Sauntee Braddock; Phone Number: 858-534-8248; Email: sbraddock@health.ucsd.edu
      • Principal Investigator: Rebecca Shatsky, MD
    • Los Angeles, California, United States, 90404
      • Recruiting
      • University California, Los Angeles
      • Principal Investigator: Saeed Sadeghi, MD
      • Contact: Monica Rocha; Phone Number: 16910 310-998-4747; Email: mprocha@mednet.ucla.edu
  • Florida
    • Port Saint Lucie, Florida, United States, 34952
      • Active, not recruiting
      • Hem-Onc Associates of the Treasure Coast
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Principal Investigator: Heather Han, MD
      • Contact: Taylor L Whann; Phone Number: 813-745-0824; Email: Taylor.LewisWhann@moffitt.org
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
      • Contact: Ashley Trumbull, MS; Phone Number: 404-778-3969; Email: Ashley.lynn.trumbull@emory.edu
      • Contact: Kathleen Coleman; Phone Number: 404.251.1278; Email: kathleen.marie.coleman@emory.edu
      • Principal Investigator: Kevin Kalinsky, MD, MS
  • Massachusetts
    • Boston, Massachusetts, United States, 02142
      • Recruiting
      • Massachusetts General Hospital
      • Principal Investigator: Seth Wander, MD
      • Contact: Amber Newton; Phone Number: 617-726-1634; Email: ANEWTON3@mgh.harvard.edu
      • Contact: Abigail Fessele; Phone Number: (P): 617-724-8305; Email: afessele@mgh.harvard.edu
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Principal Investigator: Katherine Clifton, MD
      • Contact: Sammie Ruzicka, LMSW; Phone Number: 314-747-5209; Email: ruzicka@wustl.edu
      • Contact: Tracy Summa, CCRP; Phone Number: 314.362.0263; Email: tracy.summa@wustl.edu
  • New York
    • Port Jefferson Station, New York, United States, 11776
      • Recruiting
      • New York Cancer and Blood Specialists
      • Principal Investigator: Richard Zuniga, MD
      • Contact: Laura Parisi, LPN; Phone Number: 631-675-5146; Email: lparisi@nycancer.com
      • Contact: Lauren Gianelli-Bilka, LPN; Phone Number: 631-675-5256; Email: lgianelli@nycancer.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female >/= 18 years old
2. ECOG Performance Status 0 to 1
3. Subjects must have histologically or cytologically confirmed diagnosis of ER+, HER2- ABC consistent with ASCO CAP guidelines that is locally advanced and unresectable (Stage III) or metastatic (Stage IV) BC.
4. Measurable AND evaluable lesions at baseline per RECIST v1.1.

5. Eligible subjects must meet all of the following criteria:

   • Progression after receiving 1 line of prior cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) therapy combined with HT in the MBC setting (up to 1 additional line of CDK4/6i is permitted in the post-surgical adjuvant setting);

     • Subjects must have received therapy for ≥3 months in the MBC setting, or for ≥6 months in the adjuvant setting, prior to progression

   • Progression after ≤3 lines of prior HT therapy (regardless of whether it is HT alone or in combination with other therapies)

     • Prior HT combination agents, including SERD, SERM or AI, must have received formal approval by regulatory agency.
   • ≤ 1 prior line of chemotherapy in the metastatic setting
6. Adequate organ function
7. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. Presence of visceral metastases with severe organ dysfunction as evidence by signs and symptoms, laboratory studies, lymphangitic spread and/or rapid progression of disease
2. Pregnant or planning to become pregnant
3. Prior irradiation to >25% of the bone marrow and/or inadequate bone marrow function or evidence of clinically significant end-organ damage
4. Major surgery, chemotherapy, targeted therapy, experimental agents, or radiation within 14-28 days prior to Cycle 1, Day 1
5. Active, serious medical condition that is not well controlled with locally approved medications allowed by the protocol
6. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; RGT-419B given alone as monotherapy	Drug: RGT-419B; oral capsules
Experimental: Arm B; RGT-419B in combination with Hormonal Therapy	Drug: RGT-419B in combination with hormonal therapy; RGT-419B in combination with hormonal therapy (Selective Estrogen Receptor Degrader, Selective Estrogen Receptor Modulator, or Aromatase Inhibitor)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety & Tolerability - Number of subjects with Dose-Limiting Toxicities (DLTs) at each cohort dose level in singlet and doublet therapy	Number of subjects who have a confirmed DLT at each cohort dose level in singlet and doublet study arms during the first 28-day cycle of RGT-419B treatment.	4 weeks (1 cycle)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety & Tolerability - Incidence, Severity, and Causality of all Treatment Emergent Adverse Events (TEAEs)	Incidence, severity, and causality of all TEAEs will be assessed for all patient participating from Day 1 dosing through end of study.	through study completion, an average of 1 year
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Cmax	Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification	through study completion, an average of 1 year
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Area Under Concentration-Time Curve (AUC0-t)	Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification	through study completion, an average of 1 year
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Area Under Concentration-Time Curve to Infinity (AUC0-inf)	Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification	through study completion, an average of 1 year
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Plasma Decay Half-Life (t 1/2)	Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification	through study completion, an average of 1 year
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Time to Reach Maximum Observed Plasma Concentration (Tmax)	Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification	through study completion, an average of 1 year
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Accumulation rate after multiple doses	Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification	through study completion, an average of 1 year
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Cumulative urinary excretion	Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification	through study completion, an average of 1 year
Tumor Response assessed by Investigator according to RECIST v1.1	Tumor response measured by radiologic imaging techniques at baseline and throughout the study	through study completion, an average of 1 year
QTc Interval - Changes in corrected QT interval	Number of subjects with a clinically significant increase from baseline in corrected QT (QTc) interval on repeated ECGs during RGT-419B monotherapy.	through study completion, an average of 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom Burden	Change from baseline in symptom burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) from baseline to end of treatment	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Regor Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2022
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: February 24, 2022
• First Submitted That Met QC Criteria: March 30, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Breast Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: RGT-419B_01-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No